Retroviral vectors, based on Mo-MuLV, are successfully being used as a gene delivery system, for gene transfer into mammalian cells, while host range is determined by the viral envelope glycoprotein gp-70. Although the viral envelope is species specific (ecotropic type, amphotropic type or xenotropic type), it is not tissue specific, and host cell range is limited. We are trying to change the Mo-MuLV envelope glycoprotein, in order to target the virus particle (containing recombinant vector) to specific cells, and/or to increase target cell range. These goals might be achieved by the identification and modification of the viral receptor-recognition site, which is located on the viral envelope (package) glycoprotein - the gp-70. We have demonstrated that by exchanging specific DNA sequences of the viral gp-70, between ecotropic and amphotropic types of Mo-MuLV, the host range of these retroviral packages can be interconverted. In addition, a large switch is being made, between Mo-MuLV gp-70 (and part of the gp-15), and the outer membrane domain of the Influenza virus binding and fusion envelope glycoprotein - the HA. This might allow to target the retroviral vector to any mammalian cells having on their surface gangliosides carrying N-acetyl sialic acid.